The overarching goal of this proposal is to establish and follow a cohort of ethnically diverse pregnant women and their offspring in order to longitudinally explore the hypothesis that fetal over-nutrition is associated with obesity, metabolic and cardio- vascular abnormalities in offspring. As part of the current application, we propose to test the hypothesis that programming of neonatal adiposity is driven by maternal obesity per se, in the absence of frank gestational diabetes. To determine whether there are associations between specific maternal factors and neonatal outcomes we will examine the effects of maternal obesity, diet and weight gain during pregnancy, together with specific potential mediators measured prospectively throughout pregnancy (maternal fuels, markers of insulin-resistance and inflammation). These are factors that can be targeted by future interventions. We propose to enroll a total of 1,920 pregnant women before 15 weeks of gestation and follow them prospectively through delivery in order to explore the relationships between maternal body size and behaviors during pregnancy [pre-pregnant BMI, weight gain, diet], intra-partum fuels (glucose, lipids, FFA), markers of inflammation (IL-6, TNF-?) and insulin resistance (HOMA-IR)], and infant body size (birth weight for gestational age), fatness (determined by air displacement plethysmography) and fat deposition (skinfolds). All women will have two fasting in- person visits, in early pregnancy (15-16 weeks of gestation, IPV1) and mid pregnancy (24-28 weeks of gestation, IPV2). This well characterized cohort of pregnant women will not only permit us to test important hypotheses related to programming of neonatal fatness (Aims 1 and 2), but will also be informative for the planned follow-up of the cohort of offspring assembled. To explore the relationships between maternal factors and infant metabolic markers, a random sample (N=300) of mother/infant pairs, enriched in women with GDM, will be selected to undergo a neonatal fasting blood draw protocol. Biomarkers traditionally associated with an increased risk of future cardiovascular disease, such as glucose, lipids (triglyceride, total and HDL-cholesterol, FFA), markers of insulin resistance (HOMA-IR) and insulin secretion, and markers of inflammation (TNF-?, leptin) will be explored in these newborns (Aim 3).

Public Health Relevance

A substantial increase in the prevalence of overweight and obesity among obstetric populations of all ages, racial/ethnic and socio-economic backgrounds has been reported in the last decade. Hence, maternal obesity has become an important and potentially modifiable exposure with potential programming consequences. This project offers a unique opportunity to explore a timely public health problem by testing the hypothesis that maternal obesity programs neonatal growth, fatness and metabolism, and by identifying specific mediators of these effects that can be targeted by future interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK076648-05
Application #
8520293
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Horlick, Mary
Project Start
2009-08-01
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$662,096
Indirect Cost
$229,353
Name
University of Colorado Denver
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Shapiro, Allison L B; Ringham, Brandy M; Glueck, Deborah H et al. (2017) Infant Adiposity is Independently Associated with a Maternal High Fat Diet but not Related to Niacin Intake: The Healthy Start Study. Matern Child Health J 21:1662-1668
Starling, A P; Shapiro, A L B; Sauder, K A et al. (2017) Blood pressure during pregnancy, neonatal size and altered body composition: the Healthy Start study. J Perinatol 37:502-506
Sauder, Katherine A; Kaar, Jill L; Starling, Anne P et al. (2017) Predictors of Infant Body Composition at 5 Months of Age: The Healthy Start Study. J Pediatr 183:94-99.e1
Baker 2nd, Peter R; Patinkin, Zachary; Shapiro, Allison Lb et al. (2017) Maternal obesity and increased neonatal adiposity correspond with altered infant mesenchymal stem cell metabolism. JCI Insight 2:
Baker 2nd, Peter R; Patinkin, Zachary W; Shapiro, Allison L B et al. (2017) Altered gene expression and metabolism in fetal umbilical cord mesenchymal stem cells correspond with differences in 5-month-old infant adiposity gain. Sci Rep 7:18095
Boyle, Kristen E; Patinkin, Zachary W; Shapiro, Allison L B et al. (2017) Maternal obesity alters fatty acid oxidation, AMPK activity, and associated DNA methylation in mesenchymal stem cells from human infants. Mol Metab 6:1503-1516
Shapiro, Allison L B; Sauder, Katherine A; Tregellas, Jason R et al. (2017) Exposure to maternal diabetes in utero and offspring eating behavior: The EPOCH study. Appetite 116:610-615
Moore, B F; Sauder, K A; Starling, A P et al. (2017) Exposure to secondhand smoke, exclusive breastfeeding and infant adiposity at age 5 months in the Healthy Start study. Pediatr Obes 12 Suppl 1:111-119
Starling, Anne P; Sauder, Katherine A; Kaar, Jill L et al. (2017) Maternal Dietary Patterns during Pregnancy Are Associated with Newborn Body Composition. J Nutr 147:1334-1339
Sauder, Katherine A; Koeppen, Hallie J; Shapiro, Allison L B et al. (2017) Prenatal Vitamin D Intake, Cord Blood 25-Hydroxyvitamin D, and Offspring Body Composition: The Healthy Start Study. Nutrients 9:

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